We propose to elucidate molecular interactions between the coagulation, fibrinolytic, kinin-forming and complement systems. We wish to explore the capacity of defined reaction products of these systems to activate or to injure cellular elements such as platelets, endothelial cells, mast cells and polymorphonuclear leukocytes. We intend to study intermolecular and molecule-cell interactions in isolated systems, to identify biologically active molecules and to delineate their chemical properties. Antibody molecules will be used as probes to characterize functional sites in coagulation molecules and their alteration in disease. The results of in vitro experiments will be utilized for the investigation of experimental disease models. Factors governing the initiation and course of disseminated intravascular coagulation and of experimental lipid deposition in arteries will be studied. This work will aid elucidation of the molecular and cellular events underlying the occurrence of thrombosis and the pathogenesis of blood vessel injury in man. BIBLIOGRAPHIC REFERENCES: Kolbe, W.P., and Muller-Eberhard, H.J., The membrane attack mechanism of complement. Isolation and subunit composition of the C5b-9 complex. J. Exp. Med., 141:724, 1975; Kolb, W.P., and Muller-Eberhard, H.J., Neoantigens of the membrane attack complex of human complement. Proc. Nat. Acad. Sci. USA, 72:1687, 1975.